New Therapeutic Avenues for Spinal Muscular Atrophy in Development by ISIS Pharmaceuticals, Inc.

SIS Antisense Therapy Program for Spinal Muscular Atrophy 2010 Project Update Isis Pharmaceuticals, Inc. (ISIS) is a biotechnology company in San Diego, CA, that focuses on RNA targeting therapeutics. In December 2009, ISIS announced it had added a Spinal Muscular Atrophy (SMA) Drug to its development pipeline. This drug is called ISIS-SMNRx and is specifically designed to potentially treat SMA through the correction of SMN2 RNA splicing, the low-functioning back-up gene found in all SMA patients. The first animal model results were published online in the journal Genes and Development this week. Using this approach, ISIS hopes to provide therapeutic benefit to patients with SMA.

(PRWEB) July 16, 2010 — Families of Spinal Muscular Atrophy (FSMA) – Elk Grove Village

ISIS Antisense Therapy Program for Spinal Muscular Atrophy 2010 Project Update:
Isis Pharmaceuticals, Inc. (ISIS) is a biotechnology company in San Diego, CA, that focuses on RNA targeting therapeutics. In December 2009, ISIS announced it had added a Spinal Muscular Atrophy (SMA) Drug to its development pipeline. This drug is called ISIS-SMNRx and is specifically designed to potentially treat SMA through the correction of SMN2 RNA splicing, the low-functioning back-up gene found in all SMA patients. The first animal model results were published online in the journal Genes and Development this week. Scientists at Cold Spring Harbor Laboratory (CSHL) and Isis Pharmaceuticals have substantially reduced and delayed the onset of symptoms in a mouse model of Type III SMA, a relatively mild form of the disease, by injecting the antisense oligonucleotide (ASO) into their spinal cords.

RNA is the molecule that translates information stored in our genes into proteins. By targeting RNA, the amount of disease causing proteins, such as the SMN protein that is chronically depleted in SMA, can be modulated. The primary technology used to target disease RNA is called antisense technology, where antisense oligonucleotides (ASOs) are used as the drug substance. Antisense oligonucleotides are chemically synthesized pieces of nucleic acid designed to bind to RNA in a very selective manner and thereby regulate the function of the RNA. This results in either increased or decreased amounts of the protein produced from the targeted RNA.

In the case of SMA, the antisense drug has been shown to increase the production of the SMN protein, by targeting the RNA of the SMN2 gene. The SMN2 gene is the closely related back-up gene to the SMN1 gene that is typically deleted in SMA patients. It normally produces a truncated and low-functioning form of SMN protein. The ISIS drug is designed to bind the SMN2 RNA, driving the production of full-length, functional SMN protein, by altering the RNA splicing of the SMN2 gene. This type of drug is called a splicing modulator.

Using this approach, ISIS hopes to provide therapeutic benefit to patients with SMA.

ISIS Project Timeline and Path Forward:
Dr. C. Frank Bennett, Ph.D., Senior Vice President, Research, ISIS Pharmaceuticals, states, “Our antisense drug for the treatment of SMA will be administered by an injection into the fluid that surrounds the spinal cord and brain by a process called intrathecal injection, which is used to delivery other types of drugs into the central nervous system. In animal studies, ISIS-SMNRx was shown to markedly increase the production of SMN protein in motor neurons, increase muscle strength and prolong survival in models of SMA. This drug is currently in pre-clinical development. Studies evaluating the safety and distribution of the drug in animals will begin later this year. These studies are necessary to support studies in SMA patients and will take about 1 year to complete.”

Dr. Bennett continues, “SMA is the leading genetic cause of infant mortality and has limited treatment options for patients. With Dr. Krainer’s lab at Cold Spring Harbor Laboratory, we have made significant progress in identifying a drug development candidate (for SMA) and toward conducting early preclinical studies to access its therapeutic potential. We are committed to advancing this program toward the clinic.” The first in human studies (clinical trials) will primarily be designed to test the safety of the drug in SMA patients and will be of relatively short duration. Positive data from first in human studies will allow for longer duration dosing of the drug and the assessment of possible benefit in children with SMA. Dr. C. Frank Bennett, Ph.D. was a panelist at the 2010 Families of SMA Annual Conference in Santa Clara, CA.

Please click here to read the Cold Spring Harbor Laboratory paper abstract.

Please click here to learn more about this approach on the Families of SMA (FSMA) website.

In order to commercially develop their therapeutic candidate for SMA, Isis Pharmaceuticals, Inc. exclusively licensed certain intellectual property from the University of Massachusetts. Families of SMA funded in part the early research for the foresighted program that led to this intellectual property with three grant awards of over $500,000 to Dr. Rivindra Singh and his colleagues between 2003 and 2006. The work was done in collaboration with Dr. Elliott Androphy at the University of Massachusetts.

“This program is a perfect illustration of how funding basic research often leads to new therapeutic avenues to treat SMA. This idea is one of the main tenets of the FSMA research strategy,” says Jill Jarekci, Ph.D., Research Director of FSMA.

About ISIS Pharmaceuticals: Isis is exploiting its expertise in RNA to discover and develop novel drugs for its product pipeline and for its partners. The Company has successfully commercialized the world’s first antisense drug and has 22 drugs in development. Isis’ drug development programs are focused on treating cardiovascular, metabolic, and severe neurodegenerative diseases and cancer. Isis’ partners are developing antisense drugs invented by Isis to treat a wide variety of diseases. Isis and Alnylam Pharmaceuticals are joint owners of Regulus Therapeutics Inc., a company focused on the discovery, development and commercialization of microRNA therapeutics. Isis also has made significant innovations beyond human therapeutics resulting in products that other companies, including Abbott, are commercializing. As an innovator in RNA-based drug discovery and development, Isis is the owner or exclusive licensee of approximately 1,600 issued patents worldwide. Additional information about Isis is available at www.isispharm.com.

About Families of SMA: FSMA is dedicated to creating a treatment and cure for SMA by: Funding and advancing a comprehensive research program; Supporting SMA families through networking, information and services; Improving care for all SMA patients; Educating health professionals and the public about SMA; Enlisting government support a; Embracing all touched by SMA in a caring community. At Families of SMA, expert and independent prioritization and oversight of research projects is critical. This approach ensures that FSMA funds only the most promising research, and that the funded projects are run in a professional and efficient manner under the guidance of world-class experts. www.curesma.org Contact Information: Families of SMA 925 Busse Road Elk Grove Village, IL 60007 Phone (800) 886-1762 Fax (847) 367-7623.

SOURCE: http://www.earthtimes.org

Antisense Therapy for Spinal Muscular Atrophy

Previously, we had presented an analysis claiming to have found the drug to treat spinal muscular atrophy (SMA). Apparently researchers from the Spring Harbor Laboratory (CSHL) and California-based Isis Pharmaceuticals have positively reversed symptoms of Type III SMA, which comparatively is a mild form of the disease by an antisense drug. The ASOs were infused into the fluid surrounding the brain and spinal cord.

During the research, mice with the illness were treated with minute, chemically modified pieces of RNA known as antisense oligonucleotides (ASOs) into their spinal cords. The researchers reveal that the ASO is capable of fixing the molecular mistake underlying SMA by altering a cellular editing process termed as alternative splicing. It has been assumed that deficiency of the protein levels known as Survival of Motor Neuron (SMN) in the spinal cord’s motor neurons causes SMA. These proteins appear to waste away with the muscles that may be unable to control.

CSHL Professor Adrian Krainer, Ph.D. quoted, “Validating ASO efficacy in animal models is a crucial pre-clinical step before this strategy can be applied in SMA patients. We have now successfully demonstrated this therapeutic efficacy in the mouse nervous system. Although the mice only have the mild symptoms of Type III SMA, our treatment can effectively correct them.”

Scientists revealed that patients with SMA register a lack or mutation beyond repair of the SMNI gene producing SMN protein. Although humans seem to have a second SMN-producing gene called SMN2, the gene does not appear to be an efficient backup because it produces almost negligible functional SMN protein. The scientists pointed out that this deficiency appears as a result of a mistake arising during splicing, wherein a molecular editing process kicks in after the gene’s DNA has been copied into RNA.

Frank Bennett, Ph.D., Senior Vice President of Research at Isis Pharmaceuticals explained, “SMA is the leading genetic cause of infant mortality and has limited treatment options for patients. With Dr. Krainer’s lab at Cold Spring Harbor Laboratory, we have made significant progress in identifying a drug development candidate and conducting early preclinical studies to access its therapeutic potential. We are committed to advancing this program toward the clinic.”

Generally, freshly recognized RNA molecules may be subjected to editing or splicing in order to produce a functional blueprint for protein production. The spliceosome which is cellular machinery supposedly eliminates bits of RNA called introns that may not be required. The machinery then appears to splice remaining necessary bits called exons together. But the splicing complex is ascertained to accidentally skip an exon in case of the SMN2 gene

Krainer shared, “Coaxing a patient’s cells into efficiently including this exon, instead of skipping it, is expected to decrease the severity of SMA symptoms. Our strategy to enhance exon inclusion was to disrupt or mask ‘splicing silencers’ – regions of RNA in or around the exon that impair its recognition by the cell’s splicing machinery, and thereby promote its skipping.”

Many years ago, the investigators had designed and tested synthetic molecules mainly ASOs, which can be programmed to bind to any piece of RNA according to this target RNA’s sequence of nucleotides or ‘letters’ of its genetic code. After comparing innumerable ASOs that targeted various regions in or near the skipped exon in the SMN2 RNA, the experts seemingly identified one ASO that potentially improved exon inclusion and production of functional SMN protein.

ASO molecules were injected in the bloodstream of mice carrying a human SMN2 gene revealing symptoms of type III SMA in 2008. The outcome was that although the regimen rectified SMN2 splicing in the animals’ liver and kidneys but not in spinal cord neurons-where they may be most required. The ASOs were supposedly unable to enter the blood-brain barrier and enter the spinal cord.

CSHL Research Investigator Yimin Hua, Ph.D., who spearheaded this work in Krainer’s lab enlightened, “We first showed that this ASO corrected SMN2 splicing in the test tube, and in patients’ cells grown in the lab.”

However, this limitation seems to be avoided by directly delivering ASOs into the animals’ central nervous system which is a common route of administration for other drugs like chemotherapy agents. The researchers claim that in the entire spinal cord of type III SMA mice, infusing ASOs into the fluid surrounding the brain and spinal cord resulted in an immense elevation in the levels of SMN protein in individual motor neurons.

Krainer commented, “This effect persisted for half a year after the treatment ended, indicating that the ASO is extremely stable. And equally importantly, none of the ASO doses tested triggered toxicity or inflammation in any of the mice tested.”

It was mentioned that mice with the ailment seemed to develop necrosis which are the death of cells and destruction of tissue-in adulthood. It was affirmed that no muscle weakness was reported. But the animals began to lose their tail and ears 3-4 weeks after they are born, with complete loss occurring within a few more weeks. In order to ascertain the ability of ASOs in the prevention of symptoms, the experts treated neonatal mice or 15-day-old mouse embryos with a single ASO injection.

Having employed this treatment the neonates and embryos, appeared to be protected from tail and ear necrosis and developed into adults with normal tails and ears. Providing the animals’ central nervous system with the therapeutic ASO may restrict neuronal deterioration, muscle wasting, and vascular problems in the tail and ears. The scientists were supposedly able to restore cellular SMN protein levels in these mice.

The research was published online on July 12th in Genes and Development.

SOURCE: http://www.healthjockey.com

Jake Stacey proves doctors wrong in Canvey walk

A BRAVE little boy who doctors predicted would never walk is set to lead a sponsored stroll in aid of the hospital and charity that cared for him.

Four-year-old Jake Stacey will join more than 100 friends and family, including some of his classmates from Leigh Beck nursery, on Canvey, on a walk around Canvey’s seawall.

He was diagnosed with spinal muscular dystophy in 2008.

The condition affects the nerves of the spinal cord and interferes with the link between the brain and the muscles.

It is considered one of the deadliest genetic diseases for children under the age of two.

Doctors originally believed Jake would never be able to walk due to the weakness in his legs, but thanks to the braces and with the help of a walking frame he can move on his own.

Mum Lora Stacey, 29, of Springfield Road, Canvey, said: “Originally the diagnosis was he would not be able to walk or even hold his head up.

“But Jake is proving everybody wrong. I’m proud of him.”

Jake may have to use his wheelchair for some of the walk from Waterside Farm to Canvey Island FC in Park Lane, but he will definitely be starting and finishing.

The Walking for Jake fundraiser will raise money for Great Ormond Street Hospital and the Jennifer Trust for spinal muscular atrophy.

Great Ormond Street fitted Jake’s legs with £1,000 braces to help him walk.

Lora said: “The Jennifer Trust has been wonderful.

“When we have any questions they’re always there, on the end of the phone.

“They even gave us a camcorder so we can film Jake when we go on holiday.” A charity walk organised by Lora in 2008, after Jake was diagnosed was supported by 50 people and raised almost £3,000.

About 150 walkers have already signed up to this year’s event. They will meet at Canvey football club in Park Lane on Sunday, September 12 at 10.30am.

Participants will then be taken to Waterside Leisure Centre on vintage buses provided for free by the Castle Point Transport Museum before walking back around the sea -wall to the football club.

For more information, call Lora on 07779 041524 or visit Facebook events: Walking for Jake 2010.

SOURCE: http://www.echo-news.co.uk

Family plans Sept. 20 fundraiser at Phillies game in Baby Zane’s memory

After the death of their daughter, Zane, last year, Hillary and Keith Schmid vowed to spread the word about the disease that took her life.

After fighting 5½ months, Zane succumbed to respiratory failure from spinal muscular atrophy (SMA) on June 18, 2009.

Zane was diagnosed with SMA Type 1 when she was less than 2 months old. The genetic disease results in the loss of nerves in the spinal cord, weakens the muscles connected with those nerves and gives a patient a life expectancy of one to two years.

Because SMA is not well known or understood, the Schmid family, their friends and a large, supportive community have made it their mission to change that.

Through fundraisers and events, they remember Zane by raising awareness about SMA and money to one day finding a cure for it.

With Philadelphia a city full of loyal sports fans, the next SMA fundraiser should appeal to many. And Hillary Schmid said she has Philadelphia Phillies pitcher Cole Hamels to thank for the idea.

“I pulled into the Target parking lot in January with my daughter, Avery (Zane’s twin sister),” she said. “As I was getting her out of her car seat, I noticed a guy waiting to get into the car next to me and realized it was Cole Hamels. I’m a huge Phillies fan and I thought it would be a great fundraiser; the Phillies are so popular. Cole Hamels was the inspiration.”

After calling the Phillies’ group sales office, Schmid made it her goal to sell 500 tickets for the 7:05 p.m. Monday, Sept. 20, game against the Atlanta Braves.

“If we reach 500 tickets, I will be able to get information about SMA along with photos of Zane on the big screen,” she said. “If our goal was less than 500, the only people we would be able to bring awareness to are those who bought the tickets through this fundraiser. With 500 sold, I’ll be able to post important facts and Web sites for all to see, as well as information about how to find out if you are a carrier of SMA.

“When I was pregnant, we were not told about this disease. When they offered genetic testing, SMA wasn’t on the list. However, after our efforts, now in the Main Line Health System this testing is offered because of Zane.”

An additional benefit to reaching the 500-ticket goal is Hillary Schmid would throw out the ceremonial first pitch of the game.

“That wasn’t my goal for reaching 500 tickets, but it would be a bonus and a great opportunity,” she said.

So far the group has sold more than 400 tickets. Tickets are $20 or $26 each, depending on the seating section, and net proceeds will benefit Families of Spinal Muscular Atrophy (FSMA).

The last day to buy tickets for this event is Aug. 20.

To buy tickets online, go to www.phillies.com/sma and enter the promotional code “SMA.”

Handicapped-accessible seating is available and an added highlight is that the event falls on Hatfield Phillies Franks Dollar Dog Night.

“I wanted a way to reach out to those who don’t know about this disease,” Schmid said. “I put the word out through e-mail, Facebook, on Zane’s Web site, (and) by putting fliers around town in local stores and by word of mouth. People have been so excited and supportive. Some people aren’t able to attend the game but still wanted to donate, so they have been purchasing tickets for us to give to those who made a difference in Zane’s life, such as her doctors and social workers.”

For more information, and to be a part of Spinal Muscular Atrophy Night in memory of Zane Schmid, visit www.sweetbabyzane.com.

SOURCE: http://dailylocal.com

Ben Mattlin – Looking Back On 20 Years Of Disability Rights

Ben Mattlin lives in Los Angeles, where he’s working on a memoir. He blogs at benmattlin.blogspot.com.

When I was younger, it was legal to discriminate against people like me. I was born with spinal muscular atrophy. I’ve always used a wheelchair, and my hands are too weak to scratch an itch. My parents said I could be anything I wanted when I grew up. It wasn’t quite true.

Back in the 1960s and ’70s, my parents struggled to find a decent school willing to take a handicapped kid. I assumed the problem was I wasn’t smart enough. In 1980, I entered Harvard. It was the year Harvard had to become accessible, under a forerunner of the Americans with Disabilities Act, the Rehabilitation Act of 1973. The ancient cobblestone campus proved challenging. But what really bothered me was the administration’s refusal to grant me roommates. I might impair their experience, one dean explained. Never mind how this segregation would impact mine.

The sting of discrimination worsened after graduation. No one would hire me. Once, an editor invited me to interview for a staff opening, but upon seeing me, she asked, “How would you make photocopies? I mean, you’d be here to help us, not for us to help you.”

Then, on July 26, 1990, when I was 27, the ADA became law. It didn’t get me a job. But it addressed the differences between essential and nonessential job tasks. It identified a “reasonable accommodation” from an “undue hardship” — a critical distinction for employers and public places alike. If I encountered a restaurant or store with a 6-inch threshold and no ramp, I had constructive language to use, beyond cursing or crying. Most of all, by recognizing the injustices millions of us were confronting, it provided not just legal recourse, but validation and hope.

Now, the ADA’s impact is everywhere: wheelchair lifts on city buses, signs in Braille, sign-language interpreters. Many young disabled people are growing up with a marvelous sense of belonging, entitlement and pride I never had.

Yes, there is still a long way to go. Yet in redefining the terms of disability, the ADA made us impossible to ignore. So now people should understand we’re just part of the human landscape, and we’re here to stay.

SOURCE: http://www.npr.org

How Spinal Manipulation Activates Segmental Stabilization of the Spine

The high-velocity, low-amplitude (HVLA) thrust of a spinal adjustment/manipulation has been documented to have many beneficial effects mechanically and neurologically. Recent studies have explored the impact of the HVLA thrust on the ligamentomuscular reflex and the resultant activation of the multifidus muscle in response to the sudden stretch of local spinal ligaments, joint capsules and intervertebral discs.

This reflexively mediated, rapid and unconscious stabilizing muscular response is a protective reaction to the abrupt stretch in order to prevent disruption of molecular bonds in the connective tissue matrix.

The neuromuscular neutral zone, the ligamentomuscular reflex, creep deformation, microdamage of collagen fibers and the role of the multifidus muscle in providing dynamic stability were all reviewed in my last article, “The Neuromuscular Neutral Zone, Dynamic Stability, and Injury/Pain in the Course of Everyday Activity.” (June 3 DC) Now let’s discuss how the chiropractic adjustive thrust affects these processes in beneficial ways.

Understanding the Impact of the HVLA Thrust on the Multifidus Muscle

In order to understand the impact of the HVLA thrust on multifidi, a review of a study performed on humans undergoing lumbar surgery is necessary.¹ After an incision had been made over the involved lumbar segments and while the multifidi were still intact and not yet retracted off their origins on the spinouses and laminae, the supraspinous ligament at L2-3 and L3-4 was electrically stimulated.

The researchers observed that electromyographic recordings (EMGs) from the multifidus muscle demonstrated a direct relationship of muscular contraction in response to receptor stimulation in the supraspinous ligament. The authors explained that electrical stimulation of the supraspinous ligament mechanoreceptors (MRs) resulted in a ligamentomuscular reflex that caused the multifidus to contract in order to stabilize the supraspinous ligament and prevent possible over-distraction and ligament injury.

A 2010 paper² added that the reflex contractions of multifidus and longissimus can be elicited by electrical stimulation of afferents in discs, capsules and ligaments. The discussion noted that the reflex response is greater when afferents in several tissues are stimulated simultaneously, but mentioned that reflex activation of multifidus (MF) may be initiated just by stretching the supraspinous ligament, suggesting the presence of a discrete ligamentomuscular reflex.

Moving One Bone Relative to Another Activates the Multifidus

The Solomonow paper1 described ligaments as having only a minor mechanical role in maintaining spine stability and emphasized that the muscular co-contraction of anterior and posterior muscles is the major stabilizer of the spine. Importantly, as the authors elaborate, spinal ligaments are endowed with sensory receptors and are situated in key locations sensitive to relative motion of the vertebrae, so their receptors can monitor movement and activate muscles via spinal neurons to maintain or restore stability. Stimulation of these receptors elicits reflex activity in the paraspinal muscles and contributes to maintaining spinal stability when subjected to stress.

The paper concluded that a reflex arc exists in the human spine from MRs in spinal ligaments, discs and facet joints to the multifidi and possibly other muscles. This reflex is triggered at low to moderate loads that cause relative motion of two vertebrae, causing multifidi to become active. Certainly, this description of a reflex triggered by the noninjurious application of force which causes relative motion of two vertebrae sounds decidedly familiar to practicing chiropractors. Furthermore, the paper concluded that when conditions that challenge spinal stability are detected, such as the application of a HVLA thrust, the motor control unit activates appropriate muscles to protect, restore or avoid instability.

Eight years later, another study from the same lab³ described the function of the ligamento-muscular reflex as providing a fast dose of increased joint stability when unexpected movement elicits a sudden increase in ligament tension. This very rapid protective reflex (response time: 2.5 to 5 milliseconds) indicates that it is a fast-acting, reflexively elicited motor response to prevent damage to ligaments and joints. Spinal manipulation provides precisely the high-velocity, yet noninjurious stretch of ligaments that stimulates MRs to reflexively activate the segmental stabilizing multifidus to unload rapidly stretched ligaments and joint capsules.⁴

Scientific Basis for Understanding the Influence of the Manipulative Thrust

The findings of the above studies provide a scientific basis for understanding one of the major effects of the HVLA thrust applied to dysfunctional joints. In essence, this is what happens: A joint that is injured, inflamed, degenerated, restricted in motion or painful⁵ results in reflex inhibition, delayed activation and progressive atrophy of the multifidus muscle innervated by that segment.⁶ By clinical examination, the chiropractor identifies such a lesion (subluxation / joint complex dysfunction) and then applies a HVLA thrust to the joint.

This high-velocity force rapidly stretches the segmental ligaments, joint capsules, intertransversarii and interspinales muscles, and intervertebral discs, and intensely stimulates their numerous stretch receptors. This results in ligamentomuscular reflex activation of the multifidus, which attempts to stabilize the joint and protect it from possible injury as a result of the high-velocity stretch. The segmental multifidus, which has been reflexively inhibited and is atrophying, is stimulated to contract. This may reverse the reflex inhibition, progressive atrophy, and delayed muscle response documented to occur in the segmental multifidus which overlies a dysfunctional joint; and restore dynamic function and contractility to this primary joint stabilizer.⁷

Reprinted from Brenner AK, Kiesel KB, Buscema CJ, Gill NW.

Improved activation of lumbar multifidus following spinal manipulation: a case report applying rehabilitative ultrasound imaging. J Orthop Sports Phys Ther, 2007;37(10):613-619, published online 29 May 2007.

doi:10.2519/jospt.2007.2470.

Reprinted with permission from JOSPT and its publishers, the Orthopaedic and Sports Physical Therapy sections of the American Physical Therapy Section (APTA).

A Case Report: Post-Manipulation Improved Multifidus Function

A case report⁸ of a 33-year-old man with a 21 year history of LBP and posterior thigh pain of insidious onset demonstrated this reflex activation and improved contractility of a segmental multifidus after spinal manipulation. When performing a prone upper-extremity lifting task before manipulation, the patient exhibited a reduced ability to contract his contralateral lumbar multifidus muscle, determined by objectively measuring the pre- and post-manipulation change in multifidus thickness using a validated rehabilitative ultrasound imaging approach.

However, on repeat imaging immediately after and 24 hours after spinal manipulation, thickness change during multifidus activation while performing the prone upper-extremity lifting task increased dramatically. Pre-manipulation thickening with contraction of the multifidus during the prone upper-extremity lifting task demonstrated only a 3.6 percent average change in thickness of the multifidi at L4-L5 and L5-S1, which is well below the 22 percent average increase in asymptomatic subjects. However, after spinal manipulation, there was an immediate increase in MF thickness (17.2 percent) during the upper-extremity lifting task at both L4-5 and L5-S1. This improvement was maintained and slightly increased 24 hours post-manipulation to 20.6 percent.

The pre-manipulation thickness change represents gross muscle dysfunction, but post-manipulation changes approximate normal. The improvement of dynamic muscular function post-manipulation were accompanied by clinical benefits as well. The authors conclude that the change in contractility of the multifidus observed on ultrasound imaging demonstrates possible neurophysiologic/reflexogenic effects of spinal manipulation on the multifidus muscle. As the authors interpret the findings, spinal manipulation may affect the inflow of sensory input to the central nervous system and evoke paraspinal muscle reflexes which alter central and/or peripheral neural pathways.

The Unique Effects of High-Velocity, Low-Amplitude Force

This research, along with many other studies, confirms that dysfunctional spinal joints result in inhibition and progressive atrophy of the local multifidi. This leaves the involved spinal segments unprotected, relatively unstable, and biomechanically vulnerable to injury and recurrences with minimal or no external mechanical load or stress. The application of the high-velocity, low-amplitude force of spinal manipulation generates a rapid stretching of the ligaments, joints capsules, discs and small intrinsic spinal muscles, resulting in a reflex response in the multifidus. The multifidus is reflexively activated and contracts in a region where it would otherwise be losing cross-sectional size and density.

Somehow, based on decades of clinical experience, chiropractors have observed improvements in joint function and intuitively sensed, long before the research was available, that manipulation may help reset disturbed motor programs and activate these key segmental stabilizers in regions where they are inhibited and atrophying. The findings reported above and their practical application to chiropractic care should serve to increase clinicians’ confidence in and understanding of the mechanisms and benefits unique to the specific high-velocity, low-amplitude forces produced by spinal manipulation.

References

1. Solomonow M, et al. The ligamento-muscular stabilizing system of the spine. Spine, 1998;23(23):2552-62.
2. Sanchez-Zuriaga D, Adams MA, Dolan P. Is activation of the back muscles impaired by creep or muscle fatigue? Spine, 2010;35(5):517-25.
3. Solomonow M. Sensory-motor control of ligaments and associated neuromuscular disorders. J Electromyogr Kinesiol, 2006;16:549-67.
4. Le B, Davidson B, Solomonow D, et al. Neuromuscular control of lumbar instability following static work of various loads. Muscle Nerve, 2009;39(1):71-82.
5. Seaman D, Winterstein J. Dysafferentation: a novel term to describe the neuropathophysiological effects of joint complex dysfunction. JMPT, 1998;21(4):267-80.
6. Hodges P, et al. Rapid atrophy of the lumbar multifidus follows experimental disc or nerve root injury. Spine, 2006;31(25):2926-33.
7. MacDonald D, Moseley GL, Hodges PW. Why do some patients keep hurting their back? Evidence of ongoing back muscle dysfunction during remission from recurrent back pain. Pain, 2009;142:183-8.
8. Brenner A, et al. Improved activation of lumbar multifidus following spinal manipulation: a case report applying rehabilitative ultrasound imaging. JOSPT, 2007;7:613-19.

SOURCE: http://www.dynamicchiropractic.com

Joey Jennings – Walking on Air: His Shoes Made the Man

Joey Jennings wasn’t afraid of dying. He knew his time was coming soon.

He was afraid of what might happen to his shoes.

Jennings, 32, died quietly in his sleep in this small Florida town last month from complications with muscular dystrophy, a crippling disease that robbed him physically but never dampened his enthusiasm for living, or his lifelong love affair with Air Jordan basketball shoes.

Jennings left his mother and primary caregiver with his biggest pride and joy, an amazing collection of almost 80 pairs of like-new Nike shoes — mostly Air Jordan models spanning the last 20 years.

And she doesn’t know what to do.

“He didn’t want me to just drop them off at the Goodwill store,” Lisa Shelton said last week. “We talked about it a couple times. It was like he was preparing (to die). He wanted to make sure the shoes went to kids who really understood how special they were, the status they had, to kids who would wear them proudly. I’m just not sure how to go about it.”

She was sorting through the shoes last week, spreading them throughout the modest home in which they lived, trying to make some decisions. The shoes were all different colors, all different models, some gaudy, some tasteful, some bold and some over the edge.

There was a pair that looked like Fruit Loops, another with Jordan’s thumb print on the back of the tongues, and another made of basketball leather. Her living room looked like a shoe store spanning two decades.

All of them looked like new, as if they were never worn — you don’t wear out shoes in a wheelchair — and all were children’s size 5 1/2, since his feet stopped growing very young.

“This is who he was,” she said, motioning to the couch and coffee table, where she had put a part of the collection. “This is what he lived for. Those shoes gave him an identity. He honored them. They made him somebody in the world.”

Jennings never played sports because of the spinal muscular atrophy he was born with, but he loved watching and talking and just being around sports. At school, he loved the gym. He would watch every game he could find on television. His mother often dropped him and his motorized wheelchair off at the local playground basketball courts, where he would study the games and offer coaching tips to anyone playing.

He never left his home without first selecting a pair of Air Jordans for the day, even if the shoes never would touch the ground. He never stopped buying them either, a habit that began in middle school. He spent hours on the computer, and with books, studying the new Air Jordan models each year, carefully making his selections, using birthday and Christmas money, help from uncles and aunts and grandparents.

“I couldn’t buy him shoes like this. I was a single mom trying to get by,” Shelton recalled. “We sometimes fought about it. I said, ‘Look Joey, you’re in a wheelchair. They are too expensive for us. They don’t even serve a purpose. I’ll buy you clothes and stuff, but we can’t afford to buy you these shoes.’ I used to scream at him, ‘Not another pair of shoes in the mail.’ ”

Joey wore his shoes so proudly. They gave him confidence. They were his conversation starter, serving his gregarious, outgoing nature. He liked being the center of attention, where the action was. In a wheelchair, designer jeans don’t do much. Shirts were only half seen. Joey always led with his feet, and everyone noticed.

“He used to tell me that in the mall, he didn’t want to be ‘just the guy in the wheelchair’ — that the shoes made him feel special. People would come up and talk to him, thinking this guy was somebody,” Shelton said. “It was his connection to the mainstream. He’d wear some shoes he really liked and would come home and say, ‘People think I’m somebody because of these shoes.”’

Jennings was so protective of his collection that three summers ago, when there was a hurricane threat in Florida, he made his mother pack all the shoes into the family van, fearing that their manufactured home would not withstand the storm. His shoes would still be safe in the van.

His collection is not unique. There is a “sneakerhead” culture thriving all over the world — other collectors who love their shoes, attending shows to find the newest and latest ones. Usually, though, sneakerheads have money to burn, collecting as a hobby, or just wearing out the shoes. Joey always wore his, but he never wore them out.

The last pair he bought, he had them shipped to a friend’s house in Tampa two months ago, so his mother wouldn’t know. Hours after his death, his friend called Lisa to tell her. Everyone wanted to know, “Which shoes are you going to bury him in?”

She wants to have at least one pair bronzed, and leave them at his grave site, giving his marker some distinction. Friends keep calling the house now, some asking for their favorite pair to help them remember Joey.

His friends all smiled at the funeral, not surprised to see he was being buried in a specially-designed, blue-and-orange Florida Gators casket, honoring his favorite football team.

“The casket had just come out, and one of the things that made Joey unique was that he always wanted to be the first to have something, so we thought the casket was perfect. He might have been the first to get one,” she said.

At the funeral, they all talked about the shoes, about the pink and gray ones he was wearing in the casket. They talked about his days as a mascot for youth sports teams. He wore the baseball uniform. He traveled with his high school football team. He sat on the sideline, yelling encouragement, always confident in his wheelchair, leading with his shoes.

When he got older, those shoes went to parties, to nightclubs and concerts, to MTV spring break events, always with friends who were happy he was there. At times, he was like a pirate on wheels, flirting and confident with the shoes.

“I remember his kindergarten teacher telling me once he’d probably end up as a used-car salesman,” Lisa said. “He was quite a character, and he lived for the day. He outlived a lot of people who have that disease. And I still think part of it was his makeup, and the way he felt in those shoes.”

SOURCE: http://nba.fanhouse.com

Helping hand for MontroseAccess

Tristram Peters is throwing his support behind the MontroseAccess inaugural Walk With Me fundraiser launched at the organisation’s Corinda centre last week.

The September 12 event, in partnership with Ability First Australia, aims to raise $50,000 to help provide support services for people with disabilities in Queensland.

Mr Peters has been receiving support from MontroseAccess since the age of three after being diagnosed with type 2 spinal muscular atrophy, which has confined him to an electric wheelchair.

Now 19, the third year University of Queensland Bachelor of Journalism/Arts student said he was thrilled to join Darcy Stuart and Georgia Bishop-Cash as a Walk With Me ambassador.

“I was a client for many years at MontroseAccess and this is my way of repaying the great support they have given to me and my family,’’ he said.

Mr Peters said he would use his role as a MontroseAccess ambassador to raise awareness and funding through community donations for the organisation.

MontroseAccess chief executive Darrel Bourke said the walk would be followed by an interactive open day at the Corinda centre.

To register for the Walk With Me event or to make a donation, visit www.abilityfirstaustralia.org.au.

For more information about MontroseAccess phone 3379 9200 or visit www.montroseaccess.org.au

SOURCE: http://south-west-news.whereilive.com.au

2nd Annual Zane’s Run! – A Race to the Cure for Spinal Muscular Atrophy

Hi Friends

It is time for the 2nd Annual Zane’s Run! With the help of some friends, www.zanesrun.com is up & running. You may visit the site to see pictures from last year, register for this year’s event, and view details about the event.

Now, we all know that the Phillies game is Monday, Sept. 20. Zane’s Run is six days later on the 26th. Let me explain why there are two SMA fundraisers within 1 week.

When I first called the Phillies to organize this event in April, I was given two dates- a date in May & a date in September. As you can see, I had little choice. We do not like having fundraisers so close together, let alone within 1 week. We do apologize for this. FYI- the idea is for Zane’s Run to always take place in September.

Our job as a family affected by SMA is to promote awareness and fundraise. We do not ever want to make anyone feel obligated to attend any or every event….it’s your choice! All of you have done so much as it is, and it is greatly appreciated.

ZANE’S RUN
- Sunday, Sept. 26th, 2010
- 5K & 1 mile fun run
- Begins at 9 a.m.
- Sugartown Elem.  School in Malvern, PA

Sincerely,
Hillary, Keith, and Avery-poo

SOURCE: www.zanesrun.com

Quinazoline Program Makes Progress Toward Drug Treatment for Spinal Muscular Atrophy — Families of SMA 2010 Program Update

ELK GROVE VILLAGE, IL, Jun 25, 2010 (MARKETWIRE via COMTEX) — Late last year, Families of Spinal Muscular Atrophy (FSMA) announced that it had entered into a groundbreaking exclusive license agreement with Repligen Corporation for the development of a potential treatment for Spinal Muscular Atrophy (SMA). FSMA is dedicated to creating a treatment and cure for SMA by funding and advancing comprehensive research and drug discovery programs.

The FSMA funded Quinazoline Program has had several significant milestones — the first ever pre-IND (Investigational New Drug) meeting for SMA with the FDA took place in 2009, and FSMA then obtained Orphan Drug Designation for the drug. In the next step of the process toward finding a viable treatment for SMA, the well-established biopharmaceutical company Repligen Corporation, with extensive experience in clinical development in neurological indications, now takes on responsibility and funding for clinical development of a new SMA drug.

SMA, the leading genetic killer of children under the age of two, is typically marked by the degeneration of muscle movement including the muscles that control crawling, walking, swallowing and breathing. There are no approved therapies for the treatment of SMA to date, which affects one in every 6,000 babies. One in every 40 people carry the gene that causes SMA, indicating approximately 7.5 million carriers in the United States.

“Families of SMA has made remarkable progress in defining a series of highly potent compounds which may be clinical candidates for SMA,” stated Walter C. Herlihy, President and Chief Executive Officer of Repligen Corporation. “We look forward to working with FSMA and their collaborators in the development of what we hope will be an important new treatment for SMA.”

Importance of the Quinazoline Program Through FSMA’s leadership, ten years of research has resulted in a drug candidate that is targeted to treat the underlying cause of SMA. The licensed Quinazoline compounds increase the amount of SMN protein made from the back-up gene in SMA called SMN2. In preclinical studies, the drug has been shown to efficiently cross the blood brain barrier — a critical feature for a neurological drug — and prolong survival significantly in two different mouse models of SMA.

Quinazoline Program Update – Repligen Corporation The “clinical candidate” identified by FSMA is at a pre-clinical research phase in which detailed studies of safety, pharmacology, and toxicology are being conducted. In parallel, mouse models of SMA disease are being used to document efficacy of the drug and examine what dose and dose schedule might give the best treatment result. These two lines of research will culminate in designing and seeking approval to test the drug first in healthy volunteers and then in patients. Early phase clinical trials will be conducted in adult volunteers and then patients to establish the safety and pharmacology of the drug.

“While always difficult to predict progress milestones accurately, the preclinical work and early clinical safety and pharmacology studies in healthy humans will be the focus of the program for the next 1-2 years. If successful in establishing a safe dose which is also thought to be efficacious, future studies can examine the efficacy of the drug treatment in SMA patients,” according to James Rusche, PhD, Senior Vice President, Research and Development of Repligen Corporation.

Progress Made FSMA’s first venture into drug discovery began in 2000 as a collaboration with Aurora Biosciences, since acquired by Vertex Pharmaceuticals. The initial goal of the collaboration was to develop screening tools to search for chemical compounds that could increase SMN levels from the SMN2 gene. Several compounds with the capability of doing this were discovered and one of these compound classes called Quinazolines were chemically modified at deCODE Chemistry with full funding by FSMA to optimize and generate drug-like properties. In late 2007 a clinical candidate was selected.

In August of 2009, FSMA received FDA Orphan Drug Designation for Quinazoline495, our clinical candidate in this program, for the treatment of SMA.

FSMA then conducted the first ever SMA pre-IND meeting with the FDA.

In October of 2009, Families of SMA licensed this series of compounds to Repligen Corporation for development as a potential treatment for Spinal Muscular Atrophy.

Under the guidance of drug discovery and development experts, FSMA has made investments of $13 million during the last decade to bring this groundbreaking program to the cusp of clinical development.

Importantly, the Quinazoline program also shows that SMA drug discovery is feasible! This has encouraged many others in the government and industry to invest in SMA research.

FSMA Funds Key Drug Discovery Programs One of FSMA’s primary and critical goals is to help build the size of its SMA drug pipeline, which simply means increasing the number of viable SMA candidate therapies in pre-clinical or clinical drug development. To date FSMA has been involved in five such ventures, including the groundbreaking Quinazoline Program.

Traditionally it has been difficult to attract major pharmaceutical companies to conduct research for orphan diseases like SMA, which have small patient populations with small potential for profit. Therefore FSMA has taken the strategy of providing seed funding to encourage biotech and pharmaceutical partners to engage in SMA drug research. The objective is to reduce the risk for industrial partners by simultaneously providing funding, research tools, scientific expertise, and established clinical networks. This strategy effectively lowers the barriers for embarking in SMA drug discovery bringing us closer to discovering new therapies and ultimately, a cure for SMA.

About Families of Spinal Muscular Atrophy FSMA is dedicated to creating a treatment and cure for SMA by: Funding and advancing a comprehensive research program; Supporting SMA families through networking, information and services; Improving care for all SMA patients; Educating health professionals and the public about SMA; Enlisting government support a; Embracing all touched by SMA in a caring community. www.curesma.org

About Repligen Corporation Repligen Corporation is a biopharmaceutical company in Waltham, Massachusetts that focuses on the development of innovative therapeutic drugs for unmet medical needs especially in the field of neurodegenerative disease. Repligen has licensed the compounds developed by FSMA that hold promise as a treatment for SMA.

Contact Information
Families of SMA
925 Busse Road
Elk Grove Village, IL 60007
Phone (800) 886-1762
Fax (847) 367-7623
Email Email Contact
www.curesma.org

SOURCE: www.marketwatch.com

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